We propose to use congenitally athymic (nude) mice and nude mice selectively repaired for immune responses for investigations in two general areas of immunology: 1. Nude mice and their phenotypically normal littermates will be used to study the regulation of the immune response to "thymus-independent" antigens. We have shown that thymus-derived cells are not an absolute requirement for the immune response of mice to polyvinylpyrrolidone (PVP); however, thymus-derived cells may, when present, regulate the response to PVP. We have provided evidence for the existence of amplifier cells and suppressor cells which regulate the response to PVP. By adoptive transfer of cells from mice with enhanced or suppressed responses into PVP-immunized nude mouse recipients, we hope to identify methods to enrich for suppressor and amplifier cells. Subsequently, by treating the enriched cell populations, prior to transfer into nude recipients, with antiserums specific for certain thymus-derived cell sub-sets, we hope to characterize the regulatory cells. We have shown that the PVP-specific immune response is enhanced in pregnant mice and mice treated with silica, CCl4 or concanavalin A; we will use nude mice to determine the thymus-dependence of events leading to such enhancement of immune responses. Finally, we have shown that low-dose paralysis to PVP can be induced in normal mice. We wish now to determine the thymus-dependence of this phenomenon and the role of various cells and serum factors in the induction of low-dose paralysis to PVP. 2. Nude mice and mice made pan- or class-specifically deficient in antibody production potential will be used in immunoparasitology studies. Mice deficient in antibody production potential will be produced by treatment of mice from birth with heterologous anti-immunoglobulin antiserums. Using these mice, we will evaluate the roles of various cell types and immunoglobulin classes in elimination of trypanosomes (Trypanosoma musculi) from mice.